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The patient is a Spanish speaking octogenarian who has Treatment Resistant Bipolar I Disorder with rapid cycling. In manic phases, she becomes aggressive and takes chances. Three of her siblings committed suicide in their late teens and early 20’s. The only time she has not been depressed was for eight months while caring for her dying husband ten years ago, and again, briefly, when she woke from coma 1-1/2 years ago after her most recent of many suicide attempts. She has been profoundly suicidal and lives alone with 24/7 caretakers. Her family lives one block away and keep most of her medications at their home.

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She has bilateral heel pain and longstanding pain of both knees after total knee replacement. She sleeps six hours per night, often waking three times to void, and does not nap. No daytime sleepiness. She was blinded in one eye, and has partial sight in the other due to macular degeneration dry type. She weighs 57 kg.

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Medications: She has failed every known medication. Cymbalta helped knee pain but caused her to become more depressed. Recent lithium toxicity led to the dose being lowered though blood levels were low, and she began using a walker one week ago due to vertigo. Lamotrigine was dropped from 400 to 200 mg/day, and Namenda 5 mg was started for knee pain. Azilect was discontinued eight days ago.

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On examination, she had a very flat affect. She was very attentive and responded appropriately to questions translated for her. Her daughter and son-in-law demonstrated very tender care.

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Treatment

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The patient was given a small dose of oxytocin, a hormone made in the brain. Within one hour, she mentioned wanting Italian food — a clear sign to family that her depression was beginning to respond. Ketamine nasal spray was then discussed and a total of 10 mg was tested with no change in blood pressure or heart rate. Walking the long corridor to the elevator, she commented that pain was much better. The family indicates that if her depression responds to this, it will be the first time in more than fifty years.

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The next day, family reported that instead of sleeping her usual six hours, she slept well, from 10:30 pm to 9:00 am. Symptoms began at 9:15 am. At 11:10 am, she was anxious, depressed, with suicidal ideation and knee pain was 6 on a scale of 10.

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At 11:55 am, oxytocin was given and at 12:07 pm, 20 mg ketamine was given intra-nasally. By 12:15 am, depression, anxiety, suicidality and pain were zero. There was no change in blood pressure or pulse. Relief lasted almost five hours.

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At 4:30 pm, the caretaker reported she was crying profoundly for 10 minutes. At 5:00 pm, anxiety was rated 8, depression 10, suicidal ideation 10, pain 0. Ketamine 20 mg was given at 5:50 pm, and by 6:05 she reported no anxiety, depression or suicidality and no pain.

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She returns tomorrow for her second visit. As we go forward, we will see duration of effect. She begins low dose naltrexone today after I advised her to stop tramadol a few days ago. She had been taking tramadol, a partial opioid, for pain of both knees and heels.

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In my experience prescribing ketamine for more than eleven years, it is one of the safest medications I have ever prescribed.

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My focus is on neuroinflammation and glia in the setting of chronic pain. There is tremendous overlap in pain systems and depression with strong evidence for the role of inflammation in both conditions. Ketamine is reported to be profoundly anti-inflammatory and acts more on glial receptors than its well known effect on the NMDA receptor.

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That led me to prescribe another anti-inflammatory glial modulator for depression, low dose naltrexone (LDN). LDN antagonizes the Toll-Like Receptor 4 , the glial receptor that is a major component of the innate immune system in the brain and spinal cord. LDN has helped many of my patients who had intractable pain and a case report will be added soon that details the rapid response to LDN for a person with severe suicidality.

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A review of inflammation and glia in depression was published by Yale psychiatrists in 2008 and discusses this in much greater detail.

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Patients with Treatment Resistant Bipolar Disorder have reported that ketamine and oxytocin each help depression, but the combination works far better than would be predicted. It is hoped that persons with depression will benefit as much from addition of LDN that has helped so many with intractable pain who need ketamine much less because it is so effective. Of course these are preliminary observations after only several months, but they have been deeply rewarding. Much more work needs to be done, but in my opinion, these are a few of the key medications that have brought the greatest benefit to persons who have either pain or depression.

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Third Visit

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At her third visit last week, I sent the patient back long distance under the care of her psychiatrist with instructions to continue ketamine nasal spray and oxytocin. She apologized that she had not told the truth about her response to the medications. She had reported 100% improvement because she wanted to make her family feel better. Overall, she downgraded the rating of her depression as moderately better, and felt she was not 100%, because she still did not want to be alive. I pointed out that does not mean she is depressed, simply that she does not wish to be alive, an entirely different matter. As she spoke, she was smiling throughout the meeting.

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Her family reported that she had been swimming, had walked one block to their home over the weekend, and today they tell me she has been swimming again, and plans to swim tomorrow.

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To be continued.

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The material on this site is for informational purposes only, and is not a substitute for

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NPR reported yesterday on the beneficial effects of ketamine for depression, this time reporting on a ketamine inhaler prescribed by Demitri Papolos, MD.

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Dr. Papolos is Associate Professor of Clinical Psychiatry at the Albert Einstein College of Medicine and Director of Research of the Juvenile Bipolar Research Foundation.

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He “is one of a handful of psychiatrists in the world who began to see and to speak out about the possible deleterious effects of antidepressants and stimulants in the population of children within the bipolar spectrum.”

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The boy had attempted suicide at age 5. He was hospitalized in a psychiatric unit at age 12 and strapped down in a padded room, terrified. He failed many medications for years, some made him worse, and he was literally never able to complete a meal at table with the family without flying off in a rage or someone leaving.

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in 2010, the boy tried Dr. “Papolos’ ketamine treatment. He says he’ll remember the day for the rest of his life. ‘I think we did two puffs, and I remember I sat up and I just started laughing,’ he says. Then his mother picks up the story: ‘You said you had an internal feeling of calm that you had never had before in your life. And when we came home that night, that was the first night that we ever all had dinner at the table without somebody leaving.'”

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This boy, George McCann, now at age 22 is finally able to begin a more normal life. He needs the medication only every third day. “Papolos has treated about 60 young people with ketamine so far and says all but two have had dramatic responses.”

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“The number of patients treated so far is small, and the approach is so new it hasn’t been tested by other researchers yet. Papolos says he’s hoping a study he published late last year will help persuade other researchers to try the drug on other children.”

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“In the meantime, George McCann continues to inhale a prescribed dose of ketamine every third day. The fear and anger that once dominated his life are gone, he says, adding that his mind is free now to work….”

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The relief with ketamine from the prison of mood disorders is deeply important. Severe mood disorders such as Major Depression and Bipolar Disorder can destroy the lives of patients and their loved ones. At worst, they can be lethal.

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I think the answer is we need to simplify the method of treatment using inhaled ketamine and begin to give their lives back to the patients we see. It is one of the safest medications I have ever prescribed. It does not cause weight gain or loss. It does not cause sexual dysfunction. And although it may increase sedation when used in combination with other sedating medications, at the low doses needed to treat mood disorders, I do not see ketamine interfere with other medication.

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Ketamine can relieve depression from one second to the next. And this young man needs the medication every third day. Is that too much to ask to gain a life?

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The material on this site is for informational purposes only, and is not a substitute for